This invention relates to methods and materials which have beneficial effects in promoting the healing of wounds of the eye. The methods and materials of the invention are particularly useful in promoting the healing of corneal incisions made during keratorefractive surgical procedures such as radial keratotamy. In keratorefractive surgical procedures, the methods and materials of the invention can improve the degree of refractive correction and/or provide for greater control and predictability of the results, as well as reduce scarring and improve cosmetic appearance.
Ophthalmologists have long been concerned with the treatment of vision problems caused by defects in the geometry of the eye. The most common of these problems include myopia (nearsightedness) caused by excessive corneal curvature and astigmatism, a refractive problem caused by corneal asymmetry. In recent years, a great deal of interest has developed in the use of surgical procedures--known generally as keratorefractive surgeries--which correct these conditions by surgically altering corneal geometry. If successful, such techniques offer readily apparent advantages over the conventional methods of vision correction, i.e., the use of corrective lenses such as eyeglasses or contact lenses. Corrective lenses are often inconvenient or uncomfortable to wear and are subject to loss or breakage. Contact lenses present a risk of corneal abrasion and/or infection. These problems could be avoided if reliable keratorefractive surgical procedures could be developed that produce predictable, permanent vision correction.
Radial keratotamy is a keratorefractive surgical procedure which is employed to correct myopia caused by excessive corneal curvature. In this technique, a series of incisions is made in the cornea, usually penetrating about 90 to 95% of the thickness of the cornea. The incisions, which are usually about 3 mm in length, extend along lines which radiate outwardly from the corneal center. The number of incisions may vary from as few as four to as many as 16, with 8 to 12 being commonly employed. The incisions allow the cornea to relax and to flatten out somewhat, thereby reducing or eliminating nearsightedness. Similar procedures, in which corneal incisions in directions other than radial directions, have been employed to correct some astigmatisms.
While radial keratotamy and related keratorefractive surgeries have become fairly commonplace, the results achieved using presently available techniques are not highly predictable or controllable in any given patient. In particular, the degree of correction, measured in diopters, is not well controlled and may be more or less than is needed by the particular individual, so that the operation may have to be repeated or corrective lenses may still be needed. Furthermore, the healing process usually takes from 12 to 24 months, during which time some patients experience instability in visual acuity; that is, the cornea begins to reacquire some of the curvature lost as a result of the operation. Maximum flattening of the cornea usually occurs about 2 days after surgery, with a gradual increase in curvature occurring thereafter until the incisions have healed.
Some keratotamy patients have also encountered post-operative vision problems related to scarring. In some instances, scars at the healed incision sites cause light to be reflected within the eye, resulting in a perceived glare, particularly at night. Fluctuations in visual acuity throughout the day may also result.
The aforementioned problems encountered in keratorefractive surgery are related to the manner in which the corneal incisions heal. Yet, no efforts appear to have been made to improve the results obtained in keratorefractive surgery by significantly altering the course of healing of the surgical incisions.
A number of substances have been discussed in the literature in connection with corneal wound healing. Fibronectin, a plasma and extracellular matrix glycoprotein, has been applied as a topical wound-healing agent in the treatment of wounds or defects of the epithelial layer of the cornea (see Phan, T. M. et al., ARVO 1985 Supplement to Investigative Ophthalmology & Visual Science, Vol. 26, No. 3, p. 92 (1985); Nishida et al., Arch. Ophthalmol., 101:1046-1048 (1983); Nishida et al., Ophthalmology, 92, 2, 213-216 (1985)). The appearance of fibronectin at the edges of stromal wounds in rabbit eyes was reported by Suda and coworkers. (Current Eye Research, 1, 9, 553-556 (1982)). Dweck and coworkers have reported that type IIIc collagen and fibronectin are deposited at the site of stromal wounds in rabbits T. M. et al., ARVO 1985Supplement to Investigative Ophthalmology & Visual Science, Vol. 26, No. 3, p. 92 (1985).
The mechanisms of healing of deep stromal wounds, such as the incisions made during keratorefractive surgery, are considerably more complex than those involved in epithelial wound healing and are generally not as well understood. The incisions which are made during a keratotamy exhibit V-shaped cross-sectional configurations. They penetrate through the epithelium (outer corneal layer), the basement membrane, Bowman's membrane and most of the thickness of the stroma (the thick structural layer of the cornea), leaving only Descemet's membrane and the endothelium completely intact.